Cellular processes are orchestrated by a large number of biomolecules in a spatially and temporally coordinated manner within a tiny volume. To uncover the underlying organizational principles and their functional relevance, we take microscopy visualization as the primary approach to systematically map their spatial localization, temporal dynamics and activity profiles. By combining small tags engineered from split fluorescence proteins and CRISPR/Cas9-mediated gene editing, we have enabled large-scale tagging of endogenous proteins in human cell lines for both microscopy visualization and biochemical analysis. We have further developed the deep-learning framework to connect cellular images of proteins to their amino acid sequences.