When it comes to getting inside a family, Neil Simon may be one of the greatest American playwrights. Among the most underrated. A case in point is the Old Globe’s production of his 1991 Pulitzer Prize- and Tony Award-winning “Lost in Yonkers,” which officially launched the new, 250-seat Sheryl and Harvey White Theatre Thursday, Jan. 28. The poignant comedy, set in 1942, continues through March 7. Scott Schwartz’s casting and direction of the comedy is superb. Judy Kaye portrays Grandma Kunitz, surely one of the great female roles in American theatrical literature. As a youth she escaped the Holocaust, but not without injuries, physical and psychological. These injuries, the loss of two children and a husband, and Kaye’s humane portrayal make this Grandma understandable if not sympathetic. She has raised her family by running a candy and ice cream shop below the Yonkers apartment in which she lives with her developmentally challenged child, Bella (a gut-wrenching, bravura performance by Jennifer Regan), whose body has matured, leaving her mind and judgment far behind. Bella, however, has common sense and a certain practicality to go along with her challenges. When the play opens, Grandma’s son Eddie (Spencer Rowe) is offstage in the bedroom, talking to her. It’s a rare visit. Over the years of Eddie’s marriage, his life was devoted to his recently deceased wife and his two sons, 15 ½-year-old Jay (Steven Kaplan) and 13 1/2-year-old Arty (Austyn Myers), who we find onstage complaining about the heat and wondering why their dad’s been talking to Grandma so long. Eddie was forced to borrow money from a loan shark to pay his wife’s final medical expenses, and he’s been offered a job traveling, which of course means he won’t be able to care for the boys. Grandma says no way. The loving Bella settles the matter by opening the sleeper sofa, and the boys become part of the chaotic household dominated by the bruised, first-generation immigrant woman. Eddie regretfully hits the road, with a goal of making enough money in 10 months to repay his debt. Grandma’s other grown children, shady Louie (Jeffrey M. Bender) and emotionally challenged Gert (Amanda Naughton), add flavor and substance to the family saga, which engages and informs, bringing much laughter to the audience and tears to the characters, who from youngest to oldest are brutally forthright in expressing themselves. Rather than playing for the laughs, Schwartz goes for depth. The laughs come naturally and so does understanding of how courageous survivors of this catastrophe were, leaving their countries behind, learning a new language and doing what they must to support their families. Grandma Kunitz may have damaged her children, but one is left with hope, especially for Jay and Artie, so remarkably played by Kaplan and Myers. These two young actors, one from New York, the other a San Diego lad, seem to have bonded as if they are real brothers. Associate artist Ralph Funicello creates the period flat in Yonkers, with costume design (love the crooked seams and white socks) by Alejo Vietti, lighting by Matthew McCarthy and sound by Paul Peterson. The fully trapped theater space allows Funicello to create a stairway to the candy shop and the street, making the flat appear like the little island it is. “Lost in Yonkers” plays at 7 p.m. Tuesdays and Wednesdays; 8 p.m. Thursdays through Saturdays; 2 p.m. Saturdays and Sundays; and 7 p.m. Sundays through March 7 in the Sheryl and Harvey White Theatre, at the Old Globe’s Conrad Prebys Theatre Center, 1363 Old Globe Way, Balboa Park. For tickets ($29-$62) and information, visit www.theoldglobe.org or call (619) 23-GLOBE.