In attempts to elucidate the underlying mechanisms of tumor-promoting effect of JOSD2, we found that overexpression of JOSD2 removes K6-linked polyubiquitination of LKB1, and the deubiquitination of K6 linkage of LKB1 leads to disruption of LKB1/STRAD/MO25 complex integrity, thus inhibits kinase activity of LKB1 and downstream AMPK signaling pathway, so as to induce cell proliferation. Here, JOSD2 is linked to neoplasm.