Cops5, also known as Jab1 or CSN5, is the fifth component of the constitutive photomorphogenic-9 signalosome (COPS5/Csn5) complex. It functions in multiple cellular processes, influencing various signaling pathways such as those related to cell proliferation, cell cycle, apoptosis, genomic instability, and DNA damage response (DDR) [1,2]. Dysregulation of Cops5 contributes to oncogenesis by deactivating tumor suppressors and activating oncogenes [1,2].

In mice, inactivation of Cops5 in smooth muscle cells leads to abnormal reproductive hormone homeostasis, growth retardation, reproductive and developmental disorders, and impairment of the endocrine system associated with testicular functions [4]. Conditional Cops5-deficient mice show spermatogenesis defects, failure of reproductive organ development in both sexes, and impaired skeletal development and immune functions [4]. In addition, Cops5 knockout in embryonic stem cells results in decreased expression of the pluripotency marker Nanog, proliferation defect, G2/M cell-cycle arrest, and apoptosis. Cops5 has dual roles in maintaining genomic stability of ESCs, suppressing autophagic degradation of Mtch2 to regulate cellular metabolism and reducing endogenous DNA damage, and being required for high DNA damage repair activities [3].

In conclusion, Cops5 plays essential roles in maintaining genomic stability, cell pluripotency, and normal development, especially in reproductive development. Mouse models with Cops5 knockout or conditional knockout have revealed its significant functions in these biological processes and its potential implications in related diseases, highlighting its importance as a potential therapeutic target in cancer and a key factor in reproductive and developmental disorders [1,2,3,4].