APP belongs to a family of evolutionary conserved type I membrane proteins, that includes amyloid precursor-like protein 1 and 2 (APLP1 and APLP2) [For review see (Selkoe, 2001)]. The lethality of APP/APLP2 and of APLP1/APLP2 knockout mice revealed that these proteins have crucial developmental and postnatal functions, and suggested functional redundancy between APP and APLP2 (von Koch et al., 1997; Herms et al., 2004). In the central nervous system, increase in APP expression during development overlaps with neuronal differentiation (Hung et al., 1992). Nevertheless, the physiological role(s) of APP and APP metabolites remains largely unknown. Interestingly, soluble APP (sAPP), a cleavage product released following cleavage of APP by α-secretase, has been implicated in regulation of cell proliferation(Saitoh et al., 1989; Slack et al., 1997; Schmitz et al., 2002; Meng et al., 2001; Pietrzik et al., 1998). Recent intriguing information is provided by studies suggesting that the SVZ is a major sAPP binding site, where sAPP regulates proliferation of transit amplifying (type C cells) EGF-responsive cells (Caille et al., 2004; Ohsawa et al., 1999). These cells self-renew in the presence of
