The ADP-ribosylation factor-like 4C (ARL4C or ARL7) mRNA is translated to yield ARL4C protein. ARL4C localizes to both the cell surface membrane and nucleus; however, a GDP-restricted mutant (Arl4c T27N) is mainly distributed in the cytoplasm (Engel T et al. 2004; Heo WD et al. 2006). Further, mutant constructs showed that effective plasma membrane targeting of ARL4C required an N-terminal myristoyl motif as well as a flexible C-terminal polybasic tail, which suggests that the two ends of the protein synergistically support cell surface targeting (Heo WD et al. 2006).
Cholesterol-loading or treatment with the synthetic agonists of liver X-receptors alpha (LXRα, NR1H3) and beta (LXRβ, NR1H2), such as T0901317 or GW3965, signiﬁcantly induced the expression of ARL4C in murine RAW 264.7 and human THP1 macrophage cell lines (Hong C et al. 2011; Engel T et al. 2004; Sun D et al. 2012). Similar regulation of ARL4C mRNA expression was observed in human peripheral blood-derived monocytes (Hong C et al. 2011). NR1H2 or NR1H3 stimulation ARL4C has been shown to transport cholesterol to the membrane for the ATP-binding cassette transporter A1 (ABCA1)-associated cholesterol removal (Engel T et al. 2004). Overexpression of ARL4C in HeLa cells has been shown to enhance APOA1-mediated cholesterol efflux (Engel T et al. 2004). MicroRNA miR-26 represses NR1H2,3-dependent cholesterol efflux by targeting ARL4C mRNA (Sun D et al. 2012).