Table 1.

ER stress and skin disorders

Disease	Possible mechanism of ER stress	Possible implication of ER stress in the disease pathomechanism
Darier disease	Chronic depletion of ER calcium store due to mutations in the gene encoding SERCA2 causes constitutive ER stress in keratinocytes [31]	• Abnormal trafficking of junctional components implicates in the acantholysis [30, 31] • SERCA2-induced activation of the pro-apoptotic branches of the UPR implicates in the dyskeratosis [46]
Erythrokeratoderma variabilis	Mutant Connexin 31 with defective trafficking causes UPR in keratinocytes [4, 32]	Cell death, abnormal keratinocyte differentiation and hyperproliferation [32]
Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome	POMP (proteasome maturation protein) gene mutations proteasome insufficiency induces persistent elevated ER stress in keratinocytes [11]	Abnormal terminal differentiation [11]
Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome	Mutated MBTPS2 (a membrane-embedded zinc metalloprotease)-induced impairment in the cleavage of ATF6 induces UPR in keratinocytes [34, 35]	Abnormal keratinization [34, 35]
Psoriasis	Undefined	Abnormal epidermal keratinocyte differentiation [2]
Rosacea	Various triggering factors of rosacea such as UV exposure, skin irritants, heat, and some foods induce ER stress in keratinocytes [38, 39]	Upregulation of TLR2 which triggers TLR2-KLK5-LL37 inflammatory cascade [37-39]
Vitiligo	Environmental factors which induce oxidative stress such as UV exposure and certain chemicals can induce UPR in melanocytes [5, 40, 41]	Activation of innate inflammation which triggers autoimmunity targeting melanocytes [5, 40, 41]
Melanoma	Hypoxia, hypoglycemia, genome instability,and cytotoxic compounds [7, 42]	• Cellular adaptation to ER stress can be the survival strategies of melanoma cells [6] • ER stress-induced autophagy can be a pro-survival mechanism of melanoma cells to overcome BRAF inhibitor resistance [45]