Prkd1, also known as PKCμ, encodes a serine/threonine protein kinase [4]. It is involved in various fundamental cellular functions, such as plasma membrane disruption (PMD) repair in osteocytes [2], endothelial cell-barrier integrity regulation [5], and is a downstream target in the Twist1-induced epithelial dissemination pathway [1]. It is also associated with the KRas-NF-κB pathway in pancreatic cancer [3].

In a Prkd1 transgenic mouse model (Prkd1em1) with exon 2 deletion (loss-of-function), homozygous deletion of Prkd1 led to complex congenital heart diseases (CHDs) like atrioventricular septal defects, bicuspid aortic and pulmonary valves, and was lethal. Even in heterozygotes, cardiac differences occurred [4]. In another study, Prkd1 inhibition or genetic deletion in osteocytes using an osteocyte-targeted (Dmp1-Cre) Prkd1 conditional knockout (CKO) mouse slowed PMD repair rate, impaired post-wounding cell survival, and blunted the magnitude of loading-induced increases in tibial BMD, cortical thickness, and periosteal mineralizing surface [2].

In conclusion, Prkd1 plays a vital role in heart development, PMD repair in osteocytes, and endothelial cell-barrier integrity. Mouse models, especially the Prkd1 KO and CKO mouse models, have significantly contributed to understanding its role in congenital heart diseases and bone-related biological processes.