Cherp, also known as Calcium homeostasis endoplasmic reticulum protein, has multiple functions. Structurally, it has a nuclear localization signal and arginine/serine-dipeptide repeats-like domain. It was initially thought to be involved in intracellular calcium signaling as it colocalizes with inositol 1,4,5-trisphosphate receptor (IP3R) in the endoplasmic reticulum or perinuclear region, but later research proposed it acts in the nucleus [1,5]. It is associated with the spliceosome and has importance in regulating alternative splicing, which impacts gene expression and various biological processes [1,4,5,6].

Functional studies, including knockdown experiments, have provided insights into Cherp's role. In U2OS cells, CHERP-depletion led to poly(A)+ RNAs accumulation in the nucleus, and global analysis showed Cherp regulated alternative mRNA splicing events, with intron retention being the most frequent, through interaction with U2 small nuclear ribonucleoproteins (U2 snRNPs) and U2 snRNP-related proteins [1]. In colorectal cancer tissues, CHERP and its binding partner SR140 are significantly upregulated. Knockdown of CHERP or SR140 triggers double-stranded DNA breaks and cell death, and they regulate the splicing of UPF3A, which is involved in their tumor-promoting effect [2]. In neuroblastoma cells, CHERP knockdown inhibited cell proliferation in vitro and tumorigenicity in vivo, and induced endoplasmic reticulum stress and apoptosis [3].

In conclusion, Cherp plays crucial roles in processes like alternative splicing regulation, cell cycle progression, and cell proliferation. Its dysregulation is associated with diseases such as colorectal cancer and neuroblastoma. Studies involving knockdown (functionally similar to gene knockout in revealing gene function) have been instrumental in understanding its role in these disease-related biological processes.