Molecular motors of the myosin superfamily share a generic motor domain region. They bind actin in an ATP-sensitive manner, exhibit actin-activated ATPase activity, and generate force and movement in this interaction. Many myosins, such as the members of class-18 have not been characterized in-depth. Class-18 myosins form heavy chain dimers and contain protein interaction domains outside the motor domain. Changes of otherwise highly conserved active site residues have raised the question whether myosin-18 can productively interact with ATP in the same way as other myosins. A recently described interaction of mammalian myosin-18A with the Golgi-associated phosphoprotein GOLPH3 was proposed to link the Golgi apparatus to the actin-based cytoskeleton. Here, we characterized human myosin-18A function and its interaction with GOLPH3 in vitro. We found that the interaction of the myosin-18A motor domain with actin filaments appears to be unusual, as the ADP state displays the highest actin-affinity. We performed negative-stain electron microscopy with myosin-18A motor domain decorated F-actin filaments in different nucleotide states and observed the most homogenous and continuous decoration in the ADP-state. The isolated N-terminal subdomain contains a region rich in lysine and glutamate (KE) and a PDZ module. We show that the KE-rich region displays ATP-independent binding to F-actin, whereas the PDZ module mediates the binding of myosin-18A to GOLPH3 and thereby to the Golgi apparatus. We propose that human myosin-18A connects the actin cytoskeleton with the surfaces of organelles such as the Golgi apparatus and that it can target interacting proteins or complexes to the actin cytoskeleton via its PDZ module.