Tankyrase-1 (TRF1-interacting ankyrin-related ADP-ribose polymerase 1) and the closely related homolog Tankyrase-2 arepoly(ADP-ribose) polymerases (PARPs) that co-localize and use an ankyrin-repeat domain to bind diverse proteins, including TRF-1 (telomere-repeat-binding factor 1), IRAP (insulin-responsive aminopeptidase) and TAB182. Tankyrase-1 (also known as TNKS and TNKS1) and Tankyrase-2 (also known as TNKS2, TNKL and TANK2) interact with the same set of proteins and probably mediate overlapping functions, both at telomeres and in vesicular compartments. Overexpression of Tankyrase-1 in the nucleus promotes telomere elongation, suggesting that Tankyrase 1 may regulate access of telomerase to the telomeric complex. Overexpression of Tankyrase-2 in the nucleus releases endogenous TRF1 from telomeres, establishing Tankyrase-2 as a PARP with itself and TRF1 as acceptors of ADP-ribosylation, and suggesting the possibility of a role for Tankyrase-2 at telomeres. The ankyrin (ANK) domain of Tankyrase-2 comprises five subdomains that provide redundant binding sites for IRAP. Tankyrase-2 lacks the N-terminal Histidine/Proline/Serine-rich region of Tankyrase-1, but contains a corresponding ankyrin repeat region, sterile å motif module and poly(ADP-ribose) polymerase homology domain. The gene encoding Tankyrase-2 is widely expressed, with mRNA transcripts particularly abundant in skeletal muscle and placenta.