Furthermore, in a study of human degenerated CEP tissues, the lysosomal protease tissue proteinase D (CTSD), which is secreted by CEP, induced C5 cleavage, and C5a produced by this cleavage participated in the recruitment of immune cells (e.g., monocytes) that produced inflammatory cytokines that led to TCC deposition, activating the TCC cascade, and ultimately upregulating the expression of the catabolic enzymes MMP1 and ADAMTS4 in IVD cells, leading to IVDD (67). The gene discussed is C5; the disease is tarsal-carpal coalition syndrome.