CD4 and colorectal carcinoma: TMEM258 is involved in protein synthesis, folding and trafficking.25 Previous research has demonstrated that dysregulation of TMEM258 expression can lead to endoplasmic reticulum (ER) stress, consequently triggering activation of the unfolded protein response (UPR).25 UPR is known to be beneficial to CD4+ T cells as it supports differentiation, activation, cytokine production and autophagy.26 This may explain the potential mechanism by which increased TMEM258 expression could reduce CRC risk.