PI(3)P-independent and -dependent pathways function together in a vacuolar translocation sequence to target malarial proteins to the host erythrocyte

► R to A mutation in the HT signal abrogates PI(3)P binding and HT cleavage. ► R to A mutant is exported via HT/PI(3)P-independent pathway. ► Efficiency of HT/PI(3)P-independent export pathway is 30% of that seen with the VTS. ► VTS contains PI(3)P-dependent and -independent signals to maximize export efficiency.