Cytosolic carboxypeptidase 1 (CCP1) (CCP1)

Cytosolic carboxypeptidase 1 (CCP1), also known as AGTPBP1 or NNA1, is a zinc-dependent metallocarboxypeptidase that serves as a key regulator of microtubule post-translational modifications [1, 3]. Its primary biological function is the deglutamylation of alpha- and beta-tubulin, where it removes polyglutamate side chains to maintain microtubule stability and facilitate efficient intracellular transport [1, 14]. Loss-of-function mutations in the AGTPBP1 gene are the primary cause of childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), a severe condition characterized by the progressive loss of Purkinje cells and motor neurons [3, 12]. Beyond its role in the nervous system, CCP1 is essential for spermatogenesis and has been implicated in maintaining mitochondrial integrity and chromosomal stability [1, 9]. As a therapeutic target, CCP1 is of interest for treating neurodegenerative diseases and potentially certain cancers, with research focusing on modulating its enzymatic activity to restore microtubule homeostasis [6, 16]. While specific clinical drugs are not yet established, experimental inhibitors such as celastrol and tanomastat have been identified in preclinical studies [6].

Other names

AGTPBP1NNA1ATP/GTP binding protein 1Nervous system nuclear protein induced by axotomy protein 1CONDCAATP/GTP binding carboxypeptidase 1

Inhibition of metallocarboxypeptidase activity to modulate microtubule polyglutamylation and protein turnover.