Our hypothesis is that liver derived MASP-2 but not MASP-1 provides the “second hit” and it might be essential for the AP-dependent joint damage, and its targeted intra-hepatic inhibition can lead to the attenuation of arthritis by MBL-MASP-2-dependent regulation of FD, which is predominately generated by adipocytes. The gene discussed is MASP2; the disease is Arthritis.