SMO and non-small cell lung carcinoma: Aside from the demonstrated role of HERC4 in the regulation of mammalian Smo ubiquitination and stability in cultured NIH3T3 cells and NSCLC cells (Jiang et al., 2019; Sun et al., 2019), a genome-wide screen for modifiers of Hh pathway activity in cultured cells identified a pair of genes encoding a transmembrane protein MEGF8 and a RING family E3 ligase MGRN1 whose loss-of-function resulted in an increased response to Shh due to elevated Smo levels at the cell surface and primary cilia (Kong et al., 2020).