Reg proteins constitute a conserved family in human and rodents; their production in the pancreas (including the islets of Langerhans) is induced upon β-cell damage. While some members of the family (Reg1 and islet neogenesisassociated protein, i.e. INGAP) have been implicated in β-cell replication and/or neogenesis, including from in vivo studies using transgenic and knockout mice; the roles of the other five members have yet to be characterized. Among them, Reg2 was recently proposed to serve as an autoantigen on β-cells that elicits T-cell attack in type 1 diabetes mellitus. Elucidation of their actions and identification of their molecular targets should provide insight into the biology of these proteins and lead to the design and development of novel strategies aimed at promoting the survival and function of the pancreatic islets. As the current terminology used for mammalian Reg genes/proteins is very confusing, we also proposed a uniformed classification in human and rodents through sequence alignments.