While most scientists are chasing after hot genes, many other genes are left without much attention. Actually, in 2023, the concepts of Unknome/Unknomics were brought forward to denote those un- or ill-studied genes (and their proteins). We believe that the unknome or its component genes might bear promises to any unsolved diseases or related pathological processes. This special issue should denote this neglected area and inspire more studies in it. Beside the genes in human/host, those novel genes in important human-commensal microbes could also be covered.

We invite high-quality original research and review articles on topics including, but not limited to:
· Genes, proteins, or peptides identified in last five years;
· Genes, proteins, or peptides identified earlier but had not been studied extensively (e.g. MXRA7);
· Examples of ill-known genes that were shown to play big roles in health/disease (e.g. PLD4 in autoimmune diseases);
· Example of microbial genes affecting health/diseases;
· The experience about how to make the studies of a novel gene hot;
· Methodology for studying unknown genes;
· Public database mining for discovery of unknown/novel genes and their associations with significant diseases.