•The structure and functions of human lysyl oxidase-like 2 (LOXL2) are reviewed.•Hypotheses for cofactor biogenesis and the role of Cu2+ are described.•Proposed functions of LOXL2 in breast cancer oncogenesis are emphasized.•Hypothesized functions of intracellular and secreted LOXL2 are highlighted.•Paradoxes, major gaps in knowledge, and potential inhibitory strategies are noted.Lysyl oxidase like-2 (LOXL2) belongs to the lysyl oxidase (LOX) family, which comprises Cu2+- and lysine tyrosylquinone (LTQ)-dependent amine oxidases. LOXL2 is proposed to function similarly to LOX in the extracellular matrix (ECM) by promoting crosslinking of collagen and elastin. LOXL2 has also been proposed to regulate extracellular and intracellular cell signaling pathways. Dysregulation of LOXL2 has been linked to many diseases, including cancer, pro-oncogenic angiogenesis, fibrosis and heart diseases. In this review, we will give an overview of the current understandings and hypotheses regarding the molecular functions of LOXL2.

•Human TPQ-containing CAOs and LOX(L)s are reviewed.•Mechanisms of cofactor biogenesis and oxidation of amine substrates are described.•The relevance of these enzymes to human health and disease is emphasized.•Current and potential inhibitory strategies are highlighted.Copper amine oxidases (CAOs) are a class of enzymes that contain Cu2+ and a tyrosine-derived quinone cofactor, catalyze the conversion of a primary amine functional group to an aldehyde, and generate hydrogen peroxide and ammonia as byproducts. These enzymes can be classified into two non-homologous families: 2,4,5-trihydroxyphenylalanine quinone (TPQ)-dependent CAOs and the lysine tyrosylquinone (LTQ)-dependent lysyl oxidase (LOX) family of proteins. In this review, we will focus on recent developments in the field of research concerning human CAOs and the LOX family of proteins. The aberrant expression of these enzymes is linked to inflammation, fibrosis, tumor metastasis/invasion and other diseases. Consequently, there is a critical need to understand the functions of these proteins at the molecular level, so that strategies targeting these enzymes can be developed to combat human diseases.