There is an increased risk for autoimmune diseases and/or cancers and no one is sure what causes such outcome. The vitamin D supplementation in the management of patients with rheumatic diseases and its controversary. Indeed, the beneficial effects of vitamin D on Autoimmune Diseases (ADs) and cancers remain uncertain. However, for the presence/absence of Vitamin D Receptor (VDR) within muscle, VDR might be transiently stable, similar to nuclear hormone receptor DAF-12, most closely-related to vertebrate VDR in nematode Caenorhabditis elegans; thus some findings may be inconsistent even exacerbated with different genetic backgrounds. DAF-12 has its involvement in ageing and longevity. Currently, the Rheumatoid Arthritis (RA) therapy is with a failure of anti-TNF therapy alone, but a better inhibition of human Th17-mediated synovial inflammation has been obtained alongside 1,25(OH)2D3−an active vitamin D metabolite.