Multiple extracellular factors are hypothesized to promote the differentiation 
of unstimulated and/or stimulated secretory pathways in exocrine secretory 
cells, but the identity of differentiation factors, particularly those 
organ-specific, remain largely unknown. Here, we report on the identification of 
a novel secreted glycoprotein, lacritin, that enhances exocrine secretion in 
overnight cultures of lacrimal acinar cells which otherwise display loss of 
secretory function. Lacritin mRNA and protein are highly expressed in human 
lacrimal gland, moderately in major and minor salivary glands and slightly in 
thyroid. No lacritin message or protein is detected elsewhere among more than 50 
human tissues examined. Lacritin displays partial similarity to the 
glycosaminoglycan-binding region of brain-specific neuroglycan C (32 % identity 
over 102 amino acid residues) and to the possibly mucin-like amino globular 
region of fibulin-2 (30 % identity over 81 amino acid residues), and localizes 
primarily to secretory granules and secretory fluid. The lacritin gene consists 
of five exons, displays no alternative splicing and maps to 12q13. Recombinant 
lacritin augments unstimulated but not stimulated acinar cell secretion, 
promotes ductal cell proliferation, and stimulates signaling through tyrosine 
phosphorylation and release of calcium. It binds collagen IV, laminin-1, 
entactin/nidogen-1, fibronectin and vitronectin, but not collagen I, heparin or 
EGF. As an autocrine/paracrine enhancer of the lacrimal constitutive secretory 
pathway, ductal cell mitogen and stimulator of corneal epithelial cells, 
lacritin may play a key role in the function of the lacrimal gland-corneal axis.