Amyloid beta precursor-like protein 2 (APLP-2) is a 120-170kD member of the APP family of neuronal type I transmembrane proteins. Its extracellular domain consists of an N-terminal Cys-rich domain, an Asp/Glu-rich acidic region, a Kunitz protease inhibitor (KPI) domain, and a GAG attachment site in the membrane proximal domain. APLP-2 forms both homodimers and heterodimers with APP and APLP-1. Proteolytic cleavage of APLP-2 generates peptides similar to the amyloidogenic Ab peptides and a cytoplasmic fragment that functions as a transcriptional coactivator. Alternate splicing of APLP-2 generates isoforms that lack the KPI domain or contain an insertion that prevents GAG attachment. The extracellular domain of human APLP-2 shares 81%, 93% aa sequence identity with mouse and rat APLP-2, respectively.