On the other hand, Mid-1 ubiquitinates RIC8 guanine nucleotide exchange factor A, which promotes the progression of osteoarthritis by activating p38 mitogen-activated protein kinase signaling pathway in chondrocytes, thus pointing to a protective effect of Mid-1 signaling in OA (Shen et al., 2021). Here, RIC8A is linked to osteoarthritis.