AGBL5 encodes a metallocarboxypeptidase that functions as the primary deglutamylase enzyme (CCP5) regulating tubulin glutamylation homeostasis 1. It catalyzes removal of polyglutamate side chains from α- and β-tubulin C-terminal tails by cleaving branch-point glutamates through substrate deformation-dependent recognition 2. AGBL5 also deglutamylates non-tubulin substrates, including antiviral defense proteins. Proper glutamylation balance is essential for photoreceptor ciliary architecture, intraflagellar transport protein stability, and ciliogenesis initiation 3. Pathogenic AGBL5 variants cause autosomal recessive retinitis pigmentosa (RP75), affecting approximately 1 in 4000 individuals 45. Notably, AGBL5 mutations cause syndromic RP with sensorineural hearing loss, affecting sensory cilia in both retinal and inner ear tissues 6. Loss of AGBL5 function leads to hyperglutamylation, disrupting connecting cilium structure, destabilizing the distal axoneme, and impairing ciliary function 3. Therapeutic approaches show promise: AGBL5 expression restoration or TTLL5 knockdown rescue glutamylation homeostasis and restore ciliogenesis in mutant cells 1, identifying potential treatment targets for AGBL5-associated RP.