*5.2. SHLP3*

SHLP3 is a 38 amino acids-long peptide with the sequence *H-MLGYNFSSFPCGTISIAPGFN FYRLYFIWVNGLAKVVW-OH* and has a molecular weight of 4380.15 Da. SHLP3 increases cellular ATP levels and mitochondrial oxygen consumption rate (OCR) in vitro. SHLP3 suppresses ROS generation, mediates ERK signaling, promotes adipocyte cellular differentiation, and blocks staurosporine-induced apoptosis, thereby promoting mitochondrial and cellular survival and functions. SHLP2 and SHLP3 have insulin-sensitizing effects both in vivo and in vitro, and are known to increase leptin levels. SHLP2 functions as an insulin sensitizer both peripherally and centrally as it enhances peripheral glucose uptake and inhibits glucose production in the liver. SHLP3 also increases IL-6 and MCP-1 levels.

SHLP4 increases cell proliferation in the NIT-1 and 22RV-1 cell lines in vitro. SHLP6 drastically enhances apoptotic cell death in the NIT-1 and 22RV-1 cell lines, and exerts an effect opposite of SHLP2 and SHLP3, which are cytoprotective molecules [56]. Among all the SHLPs, SHLP2 is the only peptide whose cytoprotective function has been established in AMD (Figure 3).
