Further investigating the apoptotic phenotype after the loss of PHF5A in melanoma cells, our study revealed that the knockdown of PHF5A leads to an activation of the unfolded protein response (UPR) via PERK and ATF6‐signalling pathways with an increased expression of C/EBP Homologous Protein (CHOP). Here, EIF2AK3 is linked to melanoma.