Hcfc1, encoding transcriptional co-regulator HCF-1, undergoes an unusual proteolytic maturation at its proteolysis domain. It is involved in multiple biological processes such as cell proliferation, cobalamin metabolism, and transcriptional regulation, and is crucial for normal development and cellular function [1,2]. Genetic models, especially knockout (KO) or conditional knockout (CKO) mouse models, can help to understand its function in vivo.

In mouse models, mutations in Hcfc1 and Ronin result in reduced MMACHC expression, metabolic perturbations, developmental defects similar to cblC, and reduced expression of ribosome protein-encoding genes, uncovering its role in cobalamin metabolism and ribosome biogenesis [2]. Conditional deletion of Kdm2a in mouse pre-meiotic germ cells disrupts the recruitment of HCFC1 to promoters of key meiotic genes, leading to male sterility, showing its importance in male germ cell meiotic entry and progression [3].

In conclusion, Hcfc1 is essential for cobalamin metabolism, ribosome biogenesis, and male germ cell meiosis. Mouse models have been instrumental in revealing its role in these processes and in related diseases such as cobalamin metabolism disorders and male infertility.