Chilblain lupus erythematosus is clinically classifi ed as a subtype of chronic cutaneous lupus erythematosus (CCLE) [ 1 ]. It is characterized by infl ammatory, painful lesions at acral locations, which are precipitated by cold and wet exposure. Therefore, chilblain lupus erythematosus could well have found its place in Chapter 33 “Skin Manifestations of Systemic Lupus Erythematosus.” However, the recent elucidation of the genetic basis of a rare familial form of chilblain lupus has provided novel insights into the molecular pathogenesis of lupus erythematosus [ 2 – 4 ], which have signifi cant impact on our understanding of SLE manifestations of the skin. Therefore, this chapter will provide an overview of the molecular biology of this disease phenotype below.