The cellular cytoskeleton is made up of protein polymers (filaments) that are essential in proper cell and neuronal function as well as in development. These filaments represent the roads along which most protein transport occurs inside cells. I will discuss several examples where questions about filament-cargo interactions require the development of novel mathematical modeling, analysis, and simulation. Protein cargoes such as neurofilaments and RNA molecules bind to and unbind from cellular roads called microtubules, switching between bidirectional transport, diffusion, and stationary states. Since these transport models can be analytically intractable, we have proposed asymptotic methods in the framework of partial differential equations and stochastic processes which are useful in understanding large-time transport properties. I will discuss a recent project where we use stochastic modeling to understand how filament orientations may influence sorting of cargo in dendrites during neural development and axonal injury.