Embracing macrophage complexity for research and translation.

Macrophage identity is best described as a modular combination of gene programs rather than fixed subsets or binary states.

• Why it matters: Understanding macrophage diversity is crucial because their roles in development, homeostasis, and disease are governed by complex, context-dependent behaviors that are not captured by simple classifications, impacting therapeutic strategies.
• What they did: The authors review advances in single-cell genomics, spatial profiling, epigenomics, in vivo perturbation, and computational modeling, highlighting how macrophage states are organized through modular gene programs.
• The result: Recognizing this modular architecture enables more precise macrophage annotation and suggests that therapies should target disease-associated states by identifying surface-accessible entry points and rewiring underlying programs with spatial and temporal accuracy.