Further, UBP43 is constitutively expressed in liver, cells of the monocytic lineage and within fetal spleen [29], [33], [34], and in Ubp43−/− mice the complete lack of UBP43 expression is associated with elevated ISG15-conjugation and cellular necrosis in brain that results in severe neurological disorders [12], [27], [35], [36]. Here, ISG15 is linked to nervous system disorder.