Mucus
layers (McLs) are on the front line of the human defense
system that protect us from foreign abiotic/biotic particles (e.g.,
airborne virus SARS-CoV-2) and lubricates our organs. Recently, the
impact of McLs on human health (e.g., nutrient absorption and drug
delivery) and diseases (e.g., infections and cancers) has been studied
extensively, yet their mechanisms are still not fully understood due
to their high variety among organs and individuals. We characterize
these variances as the heterogeneity of McLs, which lies in the thickness,
composition, and physiology, making the systematic research on the
roles of McLs in human health and diseases very challenging. To advance
mucosal organoids and develop effective drug delivery systems, a comprehensive
understanding of McLs’ heterogeneity and how it impacts mucus
physiology is urgently needed. When the role of airway mucus in the
penetration and transmission of coronavirus (CoV) is considered, this
understanding may also enable a better explanation and prediction
of the CoV’s behavior. Hence, in this Review, we summarize
the variances of McLs among organs, health conditions, and experimental
settings as well as recent advances in experimental measurements,
data analysis, and model development for simulations.