Sostdc1, also known as sclerostin domain-containing protein-1, is a member of the sclerostin family. It encodes a secreted 28-32 kDa protein with a cystine knot-like domain and two N-linked glycosylation sites. Sostdc1 functions as an antagonist to bone morphogenetic protein (BMP), mediating BMP signaling, and also interacts with LRP6 to mediate LRP6 and Wnt signaling, regulating cellular proliferation, differentiation, and programmed cell death. It is crucial in various tissues such as skin, intestines, brain, lungs, kidneys, and vasculature, and is essential for bone metabolism, bone density maintenance, and fracture healing in the skeletal system. It has also been linked to multiple cancer types [1].

Deletion of the Sostdc1 gene in mice led to supernumerary teeth and improved the loss of renal function in Alport syndrome, highlighting its role in tooth development and kidney function [1]. In the skeletal system, although Sostdc1 deletion alone had no measurable effects on bone envelopes, co-deletion of Sostdc1 and Sost in male mice led to high bone mass and increased cortical properties. Also, combined administration of sclerostin antibody and Sostdc1 antibody in wild-type female mice potentiated cortical bone gain [3]. In NK cell development, Sostdc1-knockout mice showed a progressive accumulation of transitional NK cells, changes in the NK cell Ly49 repertoire, and hyporesponsive NK cells against MHC class I-deficient cell targets, indicating a role in NK cell maturation and cytotoxicity [2].

In conclusion, Sostdc1 is essential for various biological processes. The Sostdc1 knockout mouse models have provided valuable insights into its role in diseases such as Alport syndrome, bone-related disorders, and NK cell-associated immune functions, demonstrating its significance in understanding disease mechanisms and potential therapeutic targets.