Cdkn2aip, also known as CARF (Collaborator of ARF), is a member of the RNA-binding protein family. It has been shown to be involved in multiple biological processes, such as stem cell pluripotency, somatic differentiation, and regulation of hepatic lipid metabolism [1,8]. It is also associated with pathways like Wnt-signaling pathway, which is crucial for spermatogonial self-renewal and proliferation [1].

Cdkn2aip-/-male mice exhibited multiple sperm head defects, age-dependent germ cell loss, synapsis failure in spermatocytes, increased apoptosis due to damaged DNA double-strand break repair and crossover formation. In vitro, knockdown of Cdkn2aip led to extended S phase, increased DNA damage and apoptosis, highlighting its importance in spermiogenesis and germ cell development [1]. In testicular seminoma, up-regulation of CDKN2AIP was associated with inhibition of tumor growth, increase in cell senescence and apoptosis, and it interacted with CARM1 and eIF4β to exert anti-tumor activity [2]. In hepatocellular carcinoma, the methylation rate of CDKN2AIP was significantly lower in the group with HCC plus liver cirrhosis compared to the liver cirrhosis only group, suggesting its potential diagnostic value [3]. In nasopharyngeal carcinoma, higher expression of CDKN2AIP was found in radioresistant cells, and knockout of it opposed the proliferation of NPC cells [4]. In osteosarcoma, circFOXP1 promoted angiogenesis by regulating the miR-127-5p/CDKN2AIP signaling pathway [5]. In hepatocellular carcinoma, NR4A3 could directly regulate the expression of CDKN2AIP at the transcriptional level, and NR4A3 overexpression suppressed cell proliferation and tumor growth [6]. In nevus sebaceous, CDKN2AIP gene was downregulated compared to normal scalp skin [7].

In conclusion, Cdkn2aip plays essential roles in various biological processes and disease conditions. Studies using gene knockout mouse models have revealed its significance in spermiogenesis, germ cell development, and in multiple cancer-related processes, such as tumor growth, apoptosis, and angiogenesis. These findings contribute to a better understanding of the underlying mechanisms of these biological processes and diseases, potentially providing new directions for diagnosis and treatment.