Mutations in Fat’s closest mammalian homolog Fat4 (FatJ) and its Ds-like ligands strongly disrupt PCP-like processes, and have in humans been associated with the multisystem defects of Hennekam and Van Maldergem syndromes (Alders et al., 2014; Mao et al., 2011; Saburi et al., 2008; Zakaria et al., 2014). Here, FAT4 is linked to van Maldergem syndrome.