*5.1. SHLP2*

SHLP2 has a molecular weight of 3017.54 Da and is 26 amino acids long with the sequence *H-MGVKFFTLSTRFFPSVQRAVPLWTNS-OH* (Figure 1). The plasma SHLP2 levels decline with age, suggesting its critical role in aging. SHLP2 stabilizes the AMD mitochondria by preserving the mitochondrial oxidative phosphorylation protein complex subunits (I-V) in AMD RPE transmitochondrial cells, and also promotes mitochondrial metabolism. This study also highlighted the potential of an exogenously added SHLP2 peptide to enhance mitochondria-specific mtGFP fluorescence staining, increase mtDNA copy numbers, and upregulate the *PGC-1*αgene, which is a master regulator of mitochondrial biogenesis [54]. This in vitro study by Nashine et al. is the first study that demonstrates an association between SHLP2 and AMD transmitochondrial RPE cells, and therefore provides a basis for further explorative studies in the field of AMD. Pretreatment with SHLP2 inhibited apoptotic cell death as evidenced by higher live cell numbers and substantive downregulation of effector caspases, namely *Caspase-3* and *Caspase-7*, in AMD RPE cells. Moreover, SHLP2 rescued and protected AMD RPE cybrid cells against amyloid-β-induced toxicity in vitro (Figure 3). Therefore, SHLP2 could be considered a potential therapeutic candidate for macular degeneration. SHLP2 also mediates chaperone-like activity, prevents the misfolding of amyloid polypeptides, and prevents neuronal cell death [55].

**Figure 3.** Effects of SHLP2 in AMD.
