Microtubule-associated proteins (MAPs) and tubulin post-translational modifications (PTMs) act as key regulatory layers on microtubules, shaping the landscape for motor-mediated lysosomal transport within cells. Distinct combinations of MAPs and PTMs define specialized microtubule subsets that differentially recruit motor proteins, thereby biasing the directionality and lysosomal positioning, which ultimately governs lysosomal functions. Here, we investigate how specific MAP-PTM combinations selectively establish intracellular traffic routes for lysosomal transport and govern its spatial organisation within the cell.