Herein, the top fifteen genes with a significant promoter hypermethylation in cancer tissues in comparison to control healthy tissues, named GPRC5D, TMPRSS11B, PIAS2, ARG1, SRPK2, AADACL2, RGPD4, SPRR3, DEGS1, TXNDC8, SH3TC1, ZPLD1, FBXO2, ATG16L1, and GRHL1 are mostly involved in different cellular enzymatic reactions and in autophagy (Table 1). The gene discussed is RGPD4; the disease is cancer.