Psmc3ip, also known as GT198 or Hop2, is a gene with multiple functions. It encodes the nuclear PSMC3-interacting protein, which functions as a co-activator of steroid hormone-mediated gene expression. It is involved in the homologous recombination process during DNA repair of double-strand breaks, particularly in the formation of meiotic D-loop before DNA strand exchange [1,6]. It also participates in pathways related to ovarian development and is potentially important for normal ovarian function [2].

In mitotic cells, depletion of Psmc3ip causes sensitivity to poly (ADP-Ribose) polymerase inhibitors (PARPi) used in cancer treatment and ionizing radiation. Psmc3ip-depleted cells accumulate toxic RAD51 foci in response to DNA damage, show impaired homology-directed DNA repair, and become PARPi sensitive, even in cells lacking both BRCA1 and TP53BP1 [1]. In hepatocellular carcinoma (HCC), knockdown of Psmc3ip blunts cell proliferation, colony formation, and xenografted tumor development, and enhances apoptosis [3]. Mutations in Psmc3ip are associated with premature ovarian insufficiency (POI), with different biallelic mutations reported in patients with primary or secondary amenorrhea [4,5].

In conclusion, Psmc3ip plays essential roles in DNA repair, especially in homologous recombination, and in ovarian function. Studies involving its depletion or mutation have revealed its significance in cancer treatment response and ovarian-related diseases, highlighting its potential as a therapeutic target in HCC and a genetic factor in POI [1,3,4,5].