LAUSR

Recent rapid progress in key technological advances, including the broader accessibility of single cell 'omic' approaches, allowed immunologists to gain important novel insights into the contributions of individual immune cells in protective immunity and immunopathologies. These insights also taught us that there is still much to uncover about the (cellular) networks underlying immune responses. For example, in the last decade, studies on a key component of innate immunity, the complement system, have defined intracellularly active complement (the complosome) as a key orchestrator of normal cell physiology. This added an unexpected facet to the biology of complement which was long considered fully explored. Here, we will summarize succinctly the known activation modes and functions of the complosome and provide a perspective on the origins of intracellular complement. We will also make a case for extending assessments of the complotype, the individual inherited landscape of common variants in complement genes, to the complosome and for re-assessing patients with known serum complement deficiencies for complosome perturbations. Finally, we will discuss where we see current opportunities and hurdles for dissecting the compartmentalization of complement activities towards a better understanding of its contributions to cellular function in health and disease. This article is protected by copyright. All rights reserved.