We identify the ADP Ribosylation Factor Like GTPase 5B (ARL5b), a small GTPase of the Rab, Arf and Arf-related (Arl) families, which recruit and activate the fusion machineries on specific compartments (Donaldson and Jackson, 2011; Lamber et al, 2019), as a key regulator of HRV16 infection and HRV16-mediated impairment of intracellular trafficking, phagolysosome biogenesis and thus bacterial clearance. The gene discussed is ARL5B; the disease is infection.