Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD) is a 956 amino acid (aa) member of the peptidase C67 protein family with a predicted molecular weight of 107 kDa. The mouse and rat CYLD orthologs share 95% and 94% aa sequence identity with the human protein, respectively. Two isoforms of CYLD have been identified, a full-length isoform and a second isoform that lacks aa 305-307 due to alternative splicing. Expression of CYLD has been reported in fetal brain as well as adult brain, heart, leukocytes, skeletal muscle, spleen, and testis. CYLD acts as a deubiquitinase and removes K63-linked Ubiquitin chains from multiple substrates including IkB, c-Jun, and c-Fos, resulting in the inhibition of NFkB and JNK signaling. In some contexts, CYLD enhances mitosis entry, and it has also been shown to delay G 1 /S phase entry suggesting that CYLD regulates multiple phases of the cell cycle. CYLD is recognized as a tumor suppressor and mutations in CYLD result in skin appendage syndromes including Brooke-Spiegle Syndrome, familial cylindromatosis, and familial trichoepitheliomas type 1.