EIF2AK3 and pachyonychia congenita: In PC, inhibiting SPHKs/S1PRs can modulate the intrinsic mitochondrial pathway or enhance endoplasmic reticulum stress to impede cancer progression primarily encompassing pathways including PERK/eIF2α, JAK2/STAT3, and FAK/Vimentin, etc. Additionally, the TCA-induced activation of S1PR2 also contributes to PC development.