AGTPBP1 is an ATP/GTP-binding metallocarboxypeptidase that catalyzes protein deglutamylation, primarily targeting tubulin and non-tubulin substrates 1. It removes polyglutamate side chains from the C-terminal tail of alpha- and beta-tubulin, specifically cleaving long-side-chains while sparing the branching point glutamate 2. The enzyme also deglutamylates non-tubulin proteins including MYLK and KLF4, with KLF4 deglutamylation promoting proteasome-mediated degradation and negatively regulating cell pluripotency 3. Biallelic AGTPBP1 variants cause childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), characterized by progressive cognitive decline, ataxia, hypotonia, and muscle weakness 4. The Purkinje cell degeneration (pcd) mouse model harboring AGTPBP1 loss-of-function mutations demonstrates cerebellar Purkinje cell loss, retinal photoreceptor degeneration, and neurodegeneration in the olfactory bulb, thalamus, and spinal cord 5. AGTPBP1 knockout impairs neuronal differentiation, induces mitochondrial dysfunction, and increases oxidative stress, with lacosamide showing promise in rescuing these deficits through CRMP2 modulation 6. Beyond neurodegeneration, AGTPBP1 mutations cause teratozoospermia with sperm head and tail defects 7, and AGTPBP1 overexpression promotes pancreatic cancer progression via ERK signaling pathway activation 8.