We found that: i. p38 and p28 are encoded by the 5′ end of the SEL1L gene; ii. p38 is up-regulated and constitutively secreted in the cancer cells, differently from the non-tumorigenic MCF10A line; iii. p28 is expressed only in the poorly differentiated SKBr3 breast cancer line; iv. ER stress/UPR strongly enhance p38 secretion in the cancer cells; v. N-terminal SEL1L is present in secretory and degradative compartments of SKBr3 and KMS11 cells, and in vesicles released into the extracellular space. The gene discussed is SEL1L; the disease is breast cancer.