We were surprised to find that in C-mem2, CTSK is a classic marker of osteoclasts and plays an important role in bone resorption (Tan et al., 2021); SPP1 and FN1 are major bone matrix proteins that can be induced by Runx2 and are essential for osteoblast differentiation and chondrocyte maturation (Komori, 2019); PRELP is a heparin/heparan sulfate-binding protein, and it has been shown that the development of osteoarthritis is associated with PRELP (Lin et al., 2022), indicating that C-mem2 actively participates in bone homeostasis regulation. Here, CTSK is linked to osteoarthritis.