CAP-GLY domain containing linker protein 3 (CLIP3 or CLIPR-59) is thought to function as an adaptor protein recruiting CYLD into the TNFR1 signaling to facilitate CYLD-mediated deubiquitination of RIPK1 in TNFalpha signaling (Fujikura D et al. 2012). CLIP3-assisted CYLD-mediated K63-deubiquitination of RIPK1 may promote caspase-8 activation to induce apoptosis by TNFalpha. The effects of CLIPR-59 knockdown on apoptosis induction by TNFalpha were more effective in human cervical cancer HeLa cells than in human alveolar basal epithelial A549 cells or human fibrosarcoma HT1080 cells. These findings suggest that the role of CLIPR-59 on TNF-alpha-induced and RIP1-mediated pro-apoptotic signaling is dependent on cell type and context (Fujikura D et al. 2012).