Abstract <p>Proteins with chaperone-like activity can play a key role in the development of age-related macular degeneration (AMD) through the regulation of oxidative stress, apoptosis, and inflammation. Recently, a new class of chaperones (heat-resistant obscure proteins (Hero)) has been identified; these proteins exhibit properties similar to other molecular chaperones. The aim of this study is to investigate the association between the genes encoding the Hero9 (BBLN) and Hero7 (SERF2) proteins and the risk of developing AMD. The case–control study included 1845 unrelated individuals from Central Russia (300 patients with AMD, 1545 controls). Genotyping of the rs2 900 262 <i>BBLN</i> and rs4 644 832 <i>SERF2</i> was performed by the real-time PCR method using allele-specific probes. The rs2 900 262 <i>BBLN</i> SNP was associated with an increased risk of AMD in patients with the dry form of the disease (effect allele <i>T</i>, OR = 2.08, 95% CI = 1.11–3.88, <i>p</i>_perm = 0.02, <i>p</i>_bonf = 0.04). The rs4 644 832 <i>SERF2</i> SNP (protective allele <i>G</i>) was associated with a later age of AMD manifestation and later involvement of the second eye in the pathology. Both studied SNPs are characterized by strong eQTL effects that influence the expression of the genes pathogenetically significant for AMD (<i>CIZ1</i>, <i>MAP1A</i>, <i>PDIA3</i>, <i>CKMT1A/B</i>, <i>STRC</i>) in the blood, vessels, and nervous system tissues. They also influence the transcription factor binding sites involved in the interleukin 9 signaling, epithelial morphogenesis, and cellular response to oxygen level.</p>