PGRMC2, progesterone receptor membrane component 2, is a heme-binding protein. It plays a crucial role in intracellular haem transport as an intracellular haem chaperone, which is essential for many physiological processes as haem is a key prosthetic group and signalling molecule. It is also involved in pathways related to adipocyte function, female fertility, and immune homeostasis, and may have implications in diseases like postmenopausal osteoporosis and cancer [1,2,3]. Genetic models, such as knockout mouse models, are valuable for studying its functions.

In adipose-specific PGRMC2-null mice, deletion of PGRMC2 in brown fat led to reduced labile haem in the nucleus, increased stability of haem-responsive transcriptional repressors, and severe mitochondrial defects, impairing adaptive thermogenesis and causing greater metabolic deterioration on a high-fat diet [1]. In Pgrmc2 knockout zebrafish, there was subfertility due to reduced oocyte maturation and decreased progestin synthesis, suggesting PGRMC2's role in regulating female fertility via ovarian receptors and steroids [2]. Heart-specific knockout (KO) mouse models showed that PGRMC2 is a cardiac pressure-volume regulator, and its deletion led to impairment in the pressure-volume relationship and progression to congestive ventricular failure under hypoxic conditions [4].

In conclusion, PGRMC2 is essential for functions in adipocytes, female reproduction, and cardiac physiology. Model-based research, especially KO/CKO mouse models, has revealed its significance in these areas, providing insights into potential therapeutic targets for metabolic diseases, female reproductive disorders, and cardiac diseases related to stress-induced heart failure.