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Regulation of mammalian cells represents a showcase of synthetic biology, which is rapidly translated towards therapeutic and biotechnological applications. In accordance with the engineering principles of synthetic biology, designable modular protein building blocks, such as coiled coils, represent a powerful toolset for designed heterodimerization used to regulate diverse processes. Our review highlights the exceptional advantages of designable coiled-coil peptides, demonstrating their remarkable versatility. They have been used to specify cellular localization, regulate transcription, construct fast responsive systems and protein secretion, fostering cell-cell interactions, and biological applications from CAR T cell regulation to genome editing.