Besides ASICs and ENaCs, adaptation of melanoma and other cancer cells to fast growth and related to it acidic environment can be connected with an activity of other receptors and intracellular messengers, that provide stemness (CD44 [33], CD133 [34]), growth, migration, and senescence regulation (Frizzled 4 [35,36]), extirpation of extracellular lactate (connexin 43 [37]), stroma remodeling, invasion, apoptosis resistance as well as gene transcription regulation (SNAI [38], NFκB [39], and STAT3 [40]). The gene discussed is FZD4; the disease is cancer.