ALG-2 was originally discovered as a pro-apoptotic protein in a genetic screen. Due to its ability to bind calcium with high affinity it was postulated to provide a link between the known effect of calcium in programmed cell death and the molecular death execution machinery. This review article discusses the current knowledge on the structure and potential function of this protein. Several putative binding partners of ALG-2 have been identified hinting to functions of ALG-2 in apoptosis and possibly also in proliferation, endocytosis and transcriptional regulation during development. Gene deletion of the well conserved ALG-2 locus in several genetic model organisms has so far not provided insights into functions and signaling pathways with ALG-2 involvement. Special focus is given to controversial data on expression and localization of ALG-2, which is mainly caused by the use of ALG-2 antibodies with different specificities.