Gas1 (Growth Arrest Specific 1) is one of six structurally unrelated proteins that were identified by their increased expression in growth-arrested cells relative to actively proliferating cells (1, 2). Following mitogenic stimulation, Gas1 expression is transcriptionally suppressed by c-Myc as cells transit from G₀ to G₁ phases of the cell cycle (3, 4). Overexpression of Gas1 prevents S phase entry and DNA synthesis (5). Gas1-mediated blockade of the cell cycle is p53-dependent but does not require the transactivating domain of p53 (6). The human Gas1 cDNA encodes a 345 amino acid (aa) precursor that includes a 39 aa signal sequence, a 279 aa mature protein, and a 27 aa C-terminal propeptide. Gas1 contains Ala-rich and Asp-rich regions as well as an RGD sequence (5). Mature human and mouse Gas1 share 85% aa sequence identity. Human Gas1 is a 40 kDa GPI-linked glycoprotein that is uniformly distributed on the cell surface (7). In contact-inhibited vascular endothelial cells, Gas1 is induced by VE-Cadherin and VEGF expression and mediates the anti-apoptotic effect of VEGF (8). In contrast, Gas1 is induced in hippocampal neurons after NMDA exposure but functions as a pro-apoptotic effector of NMDA-mediated excitotoxicity (9). Gas1 exhibits a range of developmental actions including either promoting or inhibiting growth and differentiation of somite, limb, cerebellar, and eye tissues (10 - 14). Gas1 contributes to the antagonistic effect of Wnt proteins toward Shh function by binding the N-terminal region of Shh (11). The dependence of Gas1 function on the cellular context has been addressed by suggesting that Gas1 could function as a co-receptor for GDNF family ligands (15). This speculation is supported by R&D Systems data which demonstrate direct binding of Gas1 to Artemin and Neurturin.