AGBL5

AGBL5, also known by the names CCP5 and RP75, is a gene located on chromosome 2. Its protein is a deglutamylase, meaning it removes glutamate building blocks that have been added onto other proteins. One of its main jobs is to keep the right balance of these glutamate tags on tubulin, the scaffolding protein that builds cilia. In the eye, photoreceptors — the rod and cone cells that detect light — rely on a specialized cilium called the connecting cilium to move proteins between their parts and stay healthy. When AGBL5 does not work, this balance is disturbed and the photoreceptors gradually degenerate, which is how loss of the gene is thought to lead to retinal disease.

The most commonly reported early symptom is night blindness, difficulty seeing in dim light, followed by a slow loss of peripheral vision. The age at which symptoms begin has varied among reported patients, ranging from adolescent-onset disease to a form that becomes noticeable only in adulthood. In one series from the United Arab Emirates, AGBL5 was among the causes of non-syndromic adult-onset rod-cone dystrophy, meaning disease that started at or after age 16. A rarer presentation, unilateral retinitis pigmentosa affecting mainly one eye, has also been described in a patient with AGBL5 variants. In a 2025 study of eight families, some people with AGBL5 variants had retinitis pigmentosa alongside mild-to-moderate sensorineural hearing loss, a syndromic combination not seen in earlier reports. Because these reports involve small numbers of people, an individual's own pattern and pace of vision change cannot be predicted from the gene result alone.

AGBL5-related retinal disease follows an autosomal recessive (definition: An inheritance pattern where a person needs an altered copy of a gene from both parents to be affected. Parents with only one copy are usually unaffected carriers.) pattern, which means a person typically has a disease-causing variant in both copies of the gene, one inherited from each parent. The link between AGBL5 and retinitis pigmentosa has been confirmed across multiple independent families using exome and whole-genome sequencing. In layman's terms, the genone is the entire book, which is billions of letters long. The exomeis the specific sentences that actually make sense and show you to buikd things. AGBL5 is one of many genes that can cause retinitis pigmentosa and is a relatively uncommon cause overall. The enzyme's role in maintaining tubulin and cilia is well characterized, and researchers have consistently found that disrupting it damages the photoreceptor (definition: A light-sensing cell in the retina. Rods (used for night and peripheral vision) and cones (used for color and detail) are the two types.) connecting cilium.

Because relatively few people with AGBL5 variants have been described, the full range of severity, age of onset, and progression is still being defined. Whether hearing loss is a regular feature of AGBL5 disease or occurs only in some families is not yet clear, as it was first reported in a single 2025 study. Some early reports classified AGBL5 as a candidate gene requiring further confirmation, though later work strengthened the association considerably. The precise biological steps that connect the enzyme's loss to photoreceptor (definition: A light-sensing cell in the retina. Rods (used for night and peripheral vision) and cones (used for color and detail) are the two types.) death are still being worked out, largely in animal and laboratory models rather than in people.

No approved therapy currently targets AGBL5, and the treatment status is described once here to avoid repetition. In mice lacking AGBLl5, photoreceptors accumulated too many glutamate tags on tubulin and then degenerated, with cone cells often affected earlier and more severely than rods. These animal studies showed damage to the connecting cilium and problems moving key vision proteins into place, helping explain how the disease may develop. In cultured human retinal cells engineered to lack AGBL5, researchers were able to restore normal tubulin tagging and cilia formation, either by supplying working AGBL5 or by lowering a partner enzyme called TTLL5. These are early laboratory findings that point to possible directions for future therapy and are not treatments available to patients today.

• Mouse model links excess tubulin tags to photoreceptor loss

  Animal (mouse) laboratory study.

  What was found:

  Tubulin accumulated too many glutamate tags, and the mice developed progressive cone-rod dystrophy with damaged photoreceptor outer segments, with cones affected earlier than rods.

  Why it matters:

  It clarifies a likely mechanism of vision loss and provides a model for testing future treatments.

  Limitation: Findings in mice may not fully match the human condition.

• Restoring cilia in AGBL5-deficient cells

  Laboratory cell study.

  What was found:

  Normal glutamylation and cilia formation were restored by supplying working AGBL5 or by reducing the partner enzyme TTLL5, pointing to two possible therapeutic routes.

  Why it matters:

  It identifies candidate strategies that could be explored in more advanced models.

  Limitation: Results are in cultured cells only and require testing in retinal organoids and animals before any clinical relevance.

• Confirming AGBL5 as a cause of recessive retinitis pigmentosa

  Human genetic study of multiple families.

  What was found:

  All affected individuals carried disease-causing AGBL5 variants and showed typical retinitis pigmentosa, strengthening the gene's link to the condition and highlighting the role of tubulin glutamylation in the retina.

  Why it matters:

  This work moved AGBL5 from a proposed candidate toward an established retinitis pigmentosa gene.

  Limitation: The number of families was small and the biological mechanism was not directly tested.

• AGBL5 variants with hearing loss

  Human genetic study of multiple families.

  What was found:

  All had biallelic AGBL5 variants and no changes in known deafness genes, suggesting hearing loss can be part of an AGBL5 syndrome, likely from shared cilia problems in the ear and eye.

  Why it matters:

  It is the first evidence that AGBL5 disease can extend beyond the eye to hearing.

  Limitation: It is a single study; how often hearing loss occurs with AGBL5 is not yet established.

• Adult-onset rod-cone dystrophy including AGBL5

  Human observational case series.

  What was found:

  AGBL5 was among the recurring causes, identified in three of nineteen families, illustrating that AGBL5 disease can present in adulthood.

  Why it matters:

  It broadens the recognized age range and presentation of AGBL5-related retinal disease.

  Limitation: It reflects one regional population and a small number of families.

Two considerations set AGBL5 apart from a general retinitis pigmentosa page: some families have shown accompanying hearing loss, so watching for and evaluating hearing changes may be relevant. Onset has ranged from adolescence to adulthood across reported patients, so relatives who carry variants may develop symptoms at different ages. Because inheritance is autosomal recessive (definition: An inheritance pattern where a person needs an altered copy of a gene from both parents to be affected. Parents with only one copy are usually unaffected carriers.), unaffected parents and siblings can be carriers, which is a useful point to raise in genetic counseling. Beyond these points, the general caregiver guidance shown on every gene page applies.

• Do my specific AGBL5 variants help predict whether my disease is likely to be rod-cone or cone-rod in pattern?
• Given the reports of hearing loss with AGBL5, would a baseline hearing test be worthwhile?
• How often should my retina be monitored, and which tests are most useful for tracking change?
• What does autosomal recessive inheritance mean for my children, siblings, and other relatives?
• Are there any registries or natural-history studies for AGBL5-related retinal disease I could consider?
• How can I stay informed as research on tubulin glutamylation and AGBL5 advances?

Confirming a genetic diagnosis through testing and genetic counseling can clarify the inheritance pattern and what it may mean for relatives. Because AGBL5 has been linked to hearing loss in some families, it may be worth discussing a hearing evaluation with your care team. A retinal specialist can track the condition over time using imaging and other tests to understand how your vision is changing. To explore whether any studies might be relevant, you can use RP Hope's Clinical Trials Finder with AGBL5 preselected, where eligibility would be confirmed by a study team.