The provided experimental data demonstrating that the induction of ER stress is significantly enhanced by downregulating S1P expression through the knockdown of Sphk2 or employing the SPHK2 inhibitor ABC294640, at various doses and in different human and murine PC cell lines, resulting in the increased phosphorylation of the PERK/eukaryotic initiation factor 2alpha (eIF2α) pathway and even immunogenic cell death [83]. The gene discussed is EIF2A; the disease is pachyonychia congenita.